Burkholderia sp: Identification of major clonal lineages

描述：(申请人提供)：伯克霍尔德氏菌属内的某些细菌物种能够引起严重的人类感染。马来杆菌和假鼻疽杆菌分别是扁桃体和类鼻疽病的病原体，作为生物恐怖主义的病原体最近引起了人们的关注。洋葱杆菌复合体(BCC)中的物种是新出现的医院病原体，能够在患有慢性肉芽肿病(CGD)或囊性纤维化(CF)的人中引起危及生命的感染，囊性纤维化是高加索人最常见的遗传性致死性疾病。在慢性阻塞性肺疾病中，BCC引起的呼吸道感染通常对抗菌药物治疗无效，相当一部分患者死于迅速进展的肺部恶化和脓毒症。最近的研究表明，一些BCC物种比其他物种更容易感染CF。此外，在亚种水平上，已发现某些菌株或克隆可感染多名CF患者，这表明它们具有更强的感染能力或在该人群中传播。这项研究的目标是(I)通过对大量从CF痰培养中回收的分离株进行基因分型来鉴定人类致病基底细胞癌的主要克隆谱系，以及(Ii)通过消减杂交方法鉴定这些主要克隆的特异性基因。在短期内，基因分型分析将立即对优化CF当前感染控制策略的努力产生影响。基因分型数据也是未来结果研究的先决条件，这些研究将寻求将BCC感染的菌株类型和临床病程联系起来。主要克隆特异性基因的鉴定将为研究这些基因作为伯克霍尔德氏菌毒力决定因素的潜在作用提供一条直接的途径。这项工作的长期目标是描述这些毒力决定因素在人类感染中增强BCC致病性和/或传播性的机制。这将有助于开发预防和治疗基底细胞癌感染的新策略，并将为其他呼吸道病原体的传播机制提供有价值的见解。更好地了解BCC物种的致病性也可能提供关于密切相关物种B.Mallei和B.Posomallei的毒力和人与人传播机制的及时信息。

DESCRIPTION: (provided by applicant): Certain bacterial species within the genus Burkholderia are capable of causing significant human infection. B. mallei and B. pseudomallei, the causative agents of glanders and melioidosis, respectively, have gained attention recently as agents of bioterrorism. Species within the B. cepacia complex (Bcc) are emerging nosocomial pathogens and are capable of causing life-threatening infection in persons with chronic granulomatous disease (CGD) or cystic fibrosis (CF), the most common inherited lethal disorder in Caucasians. In CF, respiratory tract infection by Bcc is generally refractory to antimicrobial therapy and a significant proportion of patients succumbs to rapidly progressive pulmonary deterioration and sepsis. Recent work indicates that some Bcc species are much more frequently involved in infection in CF than others. Furthermore, at a subspecies level, certain strains or clones have been identified that infect multiple CF patients, suggesting that they have an enhanced ability to infect or to be transmitted within this population. The goals of the proposed research are to (i) identify major clonal lineages of human disease-causing Bcc by genotyping an extensive collection of isolates recovered from CF sputum culture, and (ii) identify genes specific to these major clones by using subtractive hybridization methodology. In the short term, the genotyping analysis will have an immediate impact on efforts to optimize current infection control strategies in CF. The genotyping data are also a prerequisite to future outcomes studies that will seek to correlate strain type and clinical course of Bcc infection. The identification of genes specific to major clones will provide an immediate avenue to investigate the potential roles of these genes as virulence determinants in Burkholderia. The long-term objectives of this work are to characterize the mechanisms whereby these virulence determinants enhance the pathogenicity and/or transmissibility of Bcc in human infection. This will enable the development of novel strategies to prevent and treat Bcc infections, and will also provide valuable insights to mechanisms involved in transmission of other respiratory pathogens. A better understanding of the pathogenicity of Bcc species is also likely to provide timely information regarding the mechanisms of virulence and person-to-person transmission of the closely related species B. mallei and B. pseudomallei.